Treatment with the TROP2 ADC sac-TMT led to a 70% objective response rate and progression-free survival was “significantly improved” as compared to placebo—the second positive readout for the asset this week.
Merck’s Chinese partner Kelun-Biotech appears to have validated the use of a TROP2 ADC along with immunotherapy—specifically the best-seller Keytruda—in first line lung cancer, potentially setting a new treatment paradigm, analysts said.
But this indication will be tough to crack with plenty of competition looming, wrote Leerink Partners in a Friday morning note to investors.
Kelun revealed data from the Phase 3 OptiTROP-Lung05 study of sacituzumab tirumotecan (sac-TMT) in an abstract posted Friday ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, which will kick off on May 29 in Chicago. The ADC was tested in 413 Chinese patients who had previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC) with certain gene mutations. Sac-TMT was added to a regimen with Keytruda while the placebo group received the immunotherapy alone.
Treatment with sac-TMT led to a 70% objective response rate (ORR) and progression-free survival (PFS) was “significantly improved” as compared to placebo. Median PFS was not yet reached at the cutoff point of 10.5 months, while the group that received immunotherapy alone had a PFS of 5.7 months. Overall survival (OS) was immature but Kelun said the trend was positive.
This is the second positive readout for sac-TMT this week heading into ASCO, with Merck announcing on May 18 that the ADC demonstrated significantly better OS and PFS in patients with late-stage endometrial cancer.
Leerink was particularly impressed by the ORR rate in NSCLC, which “compares favorably” to chemo plus Keytruda. That combo achieved about 56%–58% in this population.
PFS was also strong in a subgroup of patients with high PD-L1 expression, which the firm said “confirms the superiority of the doublet over global standard-of-care” Keytruda.
The study also showed “impressive safety and low discontinuation rates,” according to Leerink.
Kelun reported that treatment-emergent adverse events grade 3 or under—severe but not immediately life-threatening side effects—occurred in more than half of patients who received sac-TMT. That’s compared to 31% of patients in the Keytruda-only group.
Plenty of competition
Leerink said the results “appear supportive of the broader TROP2 ADC + IO strategy in [first line] NSCLC . . . but this is a high bar.”
More details on the study will be showcased at the ASCO meeting—the largest gathering of oncologists in the U.S. Leerink said the discussion will get into the weeds on the true potential of the ADC-Keytruda combo. But still, the results are a positive for Merck, according to the analyst.
“For us, details in the abstract are sufficient to drive MRK upside of +5%, given sac-TMT is one of few internal programs broad enough to drive more certain growth through the Keytruda [loss of exclusivity] period and investors have been relatively lackluster about the program,” Leerink wrote.
The data release also had Leerink comparing other companies’ programs with readthrough to the ADC-immunotherapy clinical win. AstraZeneca’s Dato-DXd, for example, had a 55% ORR rate when added to Keytruda in the Phase 1b TROPION-Lung02 study—well short of the 70% rate put up by Kelun. The Daiichi Sankyo-partnered program also had higher discontinuation rates.
Leerink also considered Akeso’s ivonescimab, a China-developed asset that Summit Therapeutics is testing for the U.S. market. Ivonescimab is a VEGF-A/PD-(L)1 bispecific, rather than an ADC, but could compete with sac-TMT in the same lung indication. Leerink said the OptiTROP-Lung05 data is “neutral” for Akeso’s program, despite having higher PFS, ORR and overall survival as compared to the Phase 3 HARMONi-2 trial.
Merck is also developing a VEGF-A/PD-1 therapy called MK-2010, which could be paired with sac-TMT in a double or triple combination for first line lung cancer.
The U.S. pharma paired up with Kelun, a subsidiary of China-based Sichuan Kelun Pharmaceutical, in December 2022 with a massive licensing deal worth up to $9.3 billion. Merck nabbed seven ADC programs, with Kelun retaining rights to their development in China.
Besides lung and endometrial cancer, sac-TMT previously showed a survival benefit in gastric cancer.
